Antibacterial antiplaque oral composition

ABSTRACT

An oral composition dentifrice containing an orally acceptable vehicle, about 30-75% by weight of a dentally acceptable water-insoluble polishing agent, a substantially water-insoluble noncationic antibacterial antiplaque agent, such as 2,4,4&#39;-trichloro-2&#39;-hydroxy-diphenyl ether (triclosan) an antibacterial enhancing agent which enhances the delivery of said antibacterial agent to, and retention thereof on, oral surfaces, and a surface active agent and/or a flavoring oil.

This is a division of application Ser. No. 07/984,629, filed Dec. 2,1992, now U.S. Pat. No. 5,312,618, granted May 17, 1994, which is adivison of application Ser. No. 07/758,345, filed Sep. 9, 1991, now U.S.Pat. No. 5,192,531, granted Mar. 9, 1993, which is a continuation ofapplication Ser. No. 07/399,669, filed Aug. 25, 1989, now abandonedwhich is a continuation-in-part of application Ser. No. 07/291,712,filed Dec. 29, 1988, now U.S. Pat. No. 4,894,220, granted Jan. 16, 1990,and of application Ser. No. 07/346,258, filed May 1, 1989, now U.S. Pat.No. 5,043,154, granted Aug. 27, 1991, which are respectively acontinuation-in-part and a continuation of application Ser. No.07/008,901, filed Jan. 30, 1989, now abandoned.

This invention relates to an antibacterial antiplaque oral compositiondentifrice. More particularly, it relates to an oral compositiondentifrice containing a substantially water-insoluble noncationicantibacterial agent effective to inhibit plaque.

Dental plaque is a soft deposit which forms on teeth as opposed tocalculus which is a hard calcified deposit on teeth. Unlike calculus,plaque may form on any part of the tooth surface, particularly includingat the gingival margin. Hence, besides being unsightly, it is implicatedin the occurrence of gingivitis.

Accordingly, it is highly desirable to include antimicrobial agentswhich have been known to reduce plaque in oral compositions. Frequently,cationic antibacterial agents have been suggested. Moreover, in U.S.Pat. No. 4, 022,880 to Vinson et al, a compound providing zinc ions asan anticalculus agent is admixed with an antibacterial agent effectiveto retard the growth of plaque bacteria. A wide variety of antibacterialagents are described with the zinc compounds including cationicmaterials such as guanides and quaternary ammonium compounds as well annon-cationic compounds such as halogenated salicylanilides andhalogenated hydroxydiphenyl ethers. The noncationic antibacterialantiplaque halogenated hydroxydiphenyl ether, triclosan, has also beendescribed in combination with zinc citrate trihydrate in European PatentPublication 0161,899 to Saxton et al. Triclosan is also disclosed inEuropean Patent Publication 0271,332 to Davis as a toothpaste componentin a carrier system containing a solubilizing agent such as propyleneglycol.

The cationic antibacterial materials such as chlorhexidine, benzathoniumchloride and cetyl pyridinium chloride have been the subject greatestinvestigation as antibacterial antiplaque agents. However, they aregenerally not effective when used with anionic materials. Noncationicantibacterial materials, on the other hand, can be compatible withanionic components in an oral composition.

However, oral compositions typically are mixtures of numerous componentsand even such typically neutral materials as humectants can affectperformance of such compositions.

Moreover, even noncationic antibacterial antiplaque agents may havelimited antiplaque effectiveness with commonly used materials such aspolyphosphate anticalculus agents which are disclosed together inBritish Patent Publication 22 00551 of Gaffar et al and in EP 0251591 ofJackson et al. In commonly assigned Ser. No. 398,605 filed on even dateherewwith, titled "Antibacterial, Antiplaque Anticalculus OralComposition", it is shown that the antiplaque effectiveness is greatlyenhanced by including an antibacterial-enhancing agent (AEA) whichenhances the deliver of said antibacterial agent to, and retentionthereof on, oral surfaces, and providing optimized amounts and ratios ofpolyphosphate and AEA.

Further, even when polyphosphate anticalculus agent is not present as incommonly assigned Ser. No. 398,605 filed on even date herewith, titled"Antibacterial Antiplaque Oral Composition", antiplaque effectiveness onsoft oral tissue is optimized by including with the AEA a solubilizingmaterial which dissolves the noncationic antibacterial agent in salivawhen the polishing agent is a siliceous polishing agent present inamount of about 5-30%. Indeed, when the amount of noncationicantibacterial agent is optimized, even the special solubilizing materialis not required, as in commonly assigned Ser. No. 398,605, filed on evendate herewith, titled "Antiplaque Antibacterial Oral Composition".

It is an advantage of this invention that an oral composition dentifricecontaining an effective antiplaque amount of a substantiallywater-insoluble noncationic antibacterial antiplaque agent and said AEAto inhibit plaque formation and a dentally acceptable water-insolublepolishing agent in amount of about 30-75% is provided, whereinpolyphosphate anticalculus agent is not present.

It is an advantage of this invention that the said AEA enhance thedelivery and retention of the antibacterial agent on teeth and on softoral tissues but Examples 1 and 3 contain 0.5-2% propylene glycolwithout requiring the presence of a material which dissolves theantibacterial agent in saliva.

It is a further advantage of this invention that an antiplaque oralcomposition is provided which is directly or indirectly effective toreduce the occurrence of gingivitis.

Additional advantages of this invention will be apparent fromconsideration of the following specification.

In accordance with certain of its aspects, this invention relates to anoral composition dentifrice comprising in an orally acceptable vehicle,about 30-75% of a dentally acceptable water-insoluble polishing agent,an effective antiplaque active ingredient amount of a substantiallywater insoluble noncationic antibacterial agent, said oral compositiondentifrice comprising at least one of a surface-active agent or aflavoring oil and about 0.05-4% by weight of said AEA wherein said oralcomposition dentifrice is substantially free of polyphosophateanticalculus agent.

Typical examples of water insoluble noncationic antibacterial agentswhich are particularly desirable from considerations of antiplaqueeffectiveness, safety and formulation are:

    ______________________________________                                        Halogenated Diphenyl Ethers                                                   2',4,4'-trichloro-2'-hydroxy-diphenyl ether (Triclosan)                       2,2'-dihydroxy-5,5'-dibromo-diphenyl ether.                                   Halogenated Salicylanilides                                                   4',5-dibromosalicylanilide                                                    3,4',5-trichlorosalcylanilide                                                 3,4',5-tribromosalicylanilide                                                 2,3,3',5-tetrachlorosalicylanilide                                            3,3,3',5-tetrachlorosalicylanilide                                            3,5-dibromo-3'-trifluoromethyl salicylanilide                                 5-n-octanoyl-3'-trifluoromethyl salicylanilide                                3,5-dibromo-4'-trifluoromethyl salicylanilide                                 3,5-dibromo-3'-trifluoro methyl salicylanilide (fluorophene)                  Benzoic Esters                                                                Methyl - p-Hydroxybenzoic Ester                                               Ethyl - p-Hydroxybenzoic Ester                                                Propyl - p-Hydroxybenzoic Ester                                               Butyl - p-Hydroxybenzoic Ester                                                Halogenated Carbanilides                                                      3,4,4'-trichlorocarbanilide                                                   3-trifluoromethyl-4,4'-dichlorocarbanilide                                    3,3,4'-trichlorocarbanilide                                                   Phenolic Compounds (including phenol and its homologs,                        mono- and poly- alkyl and aromatic halo (e.g. F, Cl, Br, I)-                  phenols, resorcinol and catechol and their                                    derivatives and bisphenolic compounds). Such compounds include                inter alia:                                                                   Phenol and its Homologs                                                       Phenol                                                                        2 Methyl               Phenol                                                 3 Methyl               Phenol                                                 4 Methyl               Phenol                                                 4 Ethyl                Phenol                                                 2,4-Dimethyl           Phenol                                                 2,5-Dimethyl           Phenol                                                 3,4-Dimethyl           Phenol                                                 2,6-Dimethyl           Phenol                                                 4-n Propyl             Phenol                                                 4-n-Butyl              Phenol                                                 4-n-Amyl               Phenol                                                 4-tert-Amyl            Phenol                                                 4-n-Hexyl              Phenol                                                 4-n-Heptyl             Phenol                                                 2-Methoxy-4-(2-Propenyl)                                                                             Phenol (Eugenol)                                       2-Isopropyl-5-Methyl   Phenol (Thymol)                                        Mono- and Poly-Alkyl and Aralkyl Halophenols                                  Methyl                 p-Chlorophenol                                         Ethyl                  p-Chlorphenol                                          n-Propyl               p-Chlorophenol                                         n-Butyl                p-Chlorophenol                                         n-Amyl                 p-Chlorophenol                                         sec-Amyl               p-Chlorophenol                                         n-Hexyl                p-Chlorophenol                                         Cyclohexyl             p-Chlorophenol                                         n-Heptyl               p-Chlorophenol                                         n-Octyl                p-Chlorophenol                                         O-Chlorophenol                                                                Methyl                 o-Chlorophenol                                         Ethyl                  o-Chlorophenol                                         n-Propyl               o-Chlorophenol                                         n-Butyl                o-Chlorophenol                                         n-Amyl                 o-Chlorophenol                                         tert-Amyl              o-Chlorophenol                                         n-Hexyl                o-chlorophenol                                         n-Heptyl               o-Chloropenol                                          p-Chlorophenol                                                                o-Benzyl               p-Chlorophenol                                         o-Benzyl-m-methyl      p-Chlorophenol                                         o-Benzyl-m, m-dimethyl p-Chlorophenol                                         o-Phenylethyl          p-Chlorophenol                                         o-Phenylethyl-m-methyl p-Chlorophenol                                         3-Methyl               p-Chlorophenol                                         3,5-Dimethyl           p-Chlorophenol                                         6-Ethyl-3-methyl       p-Chlorophenol                                         6-n-Propyl-3-methyl    p-Chloraphenol                                         6-iso-propyl-3-methyl  p-Chlorophenol                                         2-Ethyl-3,5-dimethyl   p-Chlorophenol                                         6-sec Butyl-3-methyl   p-Chlorophenol                                         2-iso-Propyl-3,5-dimethyl                                                                            p-Chlorophenol                                         6-Diethylmethyl-3-methyl                                                                             p-Chlorophenol                                         6-iso-Propyl-2-ethyl-3-methyl                                                                        p-Chlorophenol                                         2-sec Amyl-3,5-dimethyl                                                                              p-Chlorophenol                                         2-Diethylmethyl-3,5-dimethyl                                                                         p-Chlorophenol                                         6-sec Octyl-3-methyl   p-Chlorophenol                                         p-Bromophenol                                                                 Methyl                 p-Bromophenol                                          Ethyl                  p-Bromophenol                                          n-Propyl               p-Bromophenol                                          n-Butyl                p-Bromophenol                                          n-Amyl                 p-Bromophenol                                          sec-Amyl               p-Bromophenol                                          n-Hexyl                p-Bromophenol                                          cyclohexyl             p-Bromophenol                                          o-Bromophenol                                                                 tert-Amyl              o-Bromophenol                                          n-Hexyl                o-Bromophenol                                          n-Propyl-m,m-Dimethyl  o-Bromophenol                                          2-Phenyl Phenol                                                               4-Chloro-2-methyl phenol                                                      4-chloro-3-methyl phenol                                                      4-chloro-3,5-dimethyl phenol                                                  2,4-dichloro-3,5-dimethyl phenol                                              3,4,5,6-tetrabromo-2-methylphenol                                             5-methyl-2-pentylphenol                                                       4-isopropyl-3-methylphenol                                                    5-chloro-2-hydroxydiphenyl methane                                            Resorcinol and Its Derivatives                                                Resorcinol                                                                    Methyl         Resorcinol                                                     Ethyl          Resorcinol                                                     n-Propyl       Resorcinol                                                     n-Butyl        Resorcinol                                                     n-Amyl         Resorcinol                                                     n-Hexyl        Resorcinol                                                     n-Heptyl       Resorcinol                                                     n-Octyl        Resorcinol                                                     n-Nonyl        Resorcinol                                                     Phenyl         Resorcinol                                                     Benzyl         Resorcinol                                                     Phenylethyl    Resorcinol                                                     Phenylpropyl   Resorcinol                                                     p-Chlorobenzyl Resorcinol                                                     5-Chloro                                                                      2,4-Dihydroxydiphenyl Methane                                                 4'-Chloro                                                                     2,4-Dihydroxydiphenyl Methane                                                 5-Bromo                                                                       2,4-Dihydroxydiphenyl Methane                                                 4'-Bromo                                                                      2,4-Dihydroxydiphenyl Methane                                                 Bisphenolic Compounds                                                         Bisphenol A                                                                   2,2'-methylene bis (4-chlorophenol)                                           2,2'-methylene bis (3,4,6-trichlorophenol) (hexachlorophene)                  2,2'-methylene bis (4-chloro-6-bromophenol)                                   bis (2-hydroxy-3,5-dichlorophenyl) sulfide                                    bis (2-hydroxy-5-chlorobenzyl) sulfide                                        ______________________________________                                    

The noncationic antibacterial agent is present in the oral compositionin an effective antiplaque amount, typically about 0.01-5% by weight,preferably about 0.03-1% and more preferably about 0.3-0.5%. Theantibacterial agent is substantially water-insoluble, meaning that itssolubility is less than about 1% by weight in water at 25° C. and may beeven less than about 0.1%.

The preferred halogenated diphenyl ether is triclosan. The preferredphenolic compounds are phenol, thymol, eugenol, hexyl resorcinol and2,2'methylene bis (4-chloro-6-bromophenol). The most preferredantibacterial antiplaque compound is triclosan. Triclosan is disclosedin aforementioned U.S. Pat. No. 4,022,880 as an antibacterial agent incombination with an anticalculus agent which provided zinc ions and inGerman Patent Disclosure 3532860 in combination with a copper compound.In European Patent Disclosure 0278744 it is disclosed in combinationwith a tooth densensitizing agent containing a source of potassium ions.It is also disclosed as an antiplaque agent in a dentifrice formulatedto contain a lamellar liquid crystal surfactant phase having a lamellarspacing of less than 6.0 nm and which may optionally contain a zinc saltin published European Patent Application 0161898 of Lane et al and in adentifrice containing zinc citrate trihydrate in published EuropeanPatent Application 0161899 to Saxton et al.

The antibacterial-enhancing agent (AEA) which enhances delivery of saidantibacterial agent to, and retention thereof on, oral surfaces, isemployed in amounts effective to achieve such enhancement within therange in the oral composition of about 0.05 to about 4%, preferablyabout 0.1% to about 3%, more preferably about 0.5% to about 2.5% byweight.

AEA polymeric materials of the present invention include those which canbe characterized as having utility as dentifrice adhesives or fixativesor dental cements. For example, U.S. Pat. Nos. 4,521,551 and 4,375,036,each to Chang et al, describe commercially available copolymer ofmethylvinyl ether-maleic anhydride (Gantrez) as a denture fixative.However, there has not been recognition in the prior art that adhesives,fixatives or cements when applied in water soluble or water swellableform together with substantially water insoluble non-cationicantibacterial antiplaque agents could enhance the antibacterial activityof such agents. Further, in U.S. Pat. No. 4,485,090 to Chang, Gantrez ANcopolymer is mentioned among polymeric anionic membrane-formingmaterials which attach to a tooth surface to form a hydrophobic barrierwhich reduces elution of a previously applied therapeutic cariesprophylactic fluoride compound. Again, there is no recognition that suchpolymeric material could enhance the antibacterial activity ofsubstantially water insoluble non-cationic antibacterial antiplaqueagents.

This AEA may be a simple compound, preferably a polymerizable monomore,more preferably a polymer, which latter term is entirely generic,including for example oligomers, homopolymers, copolymers of two or moremonomers, block copolymers, graft copolymers, cross-linked polymers andcopolymers, and the like. The AEA may be natural or synthetic, and waterinsoluble or preferably water (saliva) soluble or swellable (hydratable,hydrogel forming). It has an (weight) average molecular weight of about100 to about 1,000,000, preferably about 1,000 to about 1,000,000, morepreferably about 2,000 or 2,500 to about 250,000 or 500,000.

The AEA ordinarily contains at least one delivery-enhancing group, whichis preferably acidic such as sulfonic, phosphinic, or more preferablyphosphonic or carboxylic, or salt thereof, e.g. alkali metal orammonium, and at least one organic retention-enhancing group, preferablya plurality of both the delivery-enhancing and retention-enhancinggroups, which latter groups preferably have the formula --(X)_(n) --Rwherein X is O, N, S, SO, SO₂, P, PO or Si or the like, R is hydrophobicalkyl, alkenyl, acyl, aryl, alkary, aralkyl, heterocyclic or theirinert-substituted derivatives, and n is zero or 1 or more. The aforesaid"inert-substituted derivatives", are intended to include substituents onR which are generally non-hydrophilic and do no significantly interferewith the desired functions of the AEA as enhancing the delivery of theantibacterial agent to, and retention thereof on, oral surfaces such ashalo, e.g. Cl, Br, I, and carbo and the like. Illustrations of suchretention-enhancing groups are tabulated below.

    ______________________________________                                        n   X                                                                         (X).sub.n R                                                                   ______________________________________                                        0   --     methyl, ethyl, propyl, butyl, isobutyl, t-buryl,                              cyclohexyl, allyl, benzyl, phenyl, chlorophenyl, xylyl,                       pyridyl, furanyl, acetyl, benzoyl, butyryl,                                   terephthaloyl, etc.                                                1   0      ethoxy, benzyloxy, thioacetoxy, phenoxy,                                      carboethoxy, carbobenzyloxy, etc.                                      N      ethylamino, diethylamino, propylamido, benzylamino,                           benzoylamido, phenylacetamido, etc.                                    S      thiobutyl, thioisobutyl, thioallyl, thiobenzyl,                               thiophenyl, thiopropionyl, phenylthioacetyl,                                  thiobenzoyl, etc.                                                      SO     butylsulfoxy, allylsulfoxy, benzylsulfoxy,                                    phenylsulfoxy, etc.                                                    SO.sub.2                                                                             butylsulfonyl, allysulfonyl, benzylsulfonyl,                                  phenylsulfonyl, etc.                                                   P      diethyphosphinyl, ethylvinylphosphinyl,                                       ethylallylphosphinyl, ethylbenzylphosphinyl,                                  ethylphenylphosphinyl, etc.                                            PO     diethylphosphinoxy, ethylvinylphosphinoxy,                                    methylallylphosphinoxy, methylbenzyphosphinoxy,                               methylphenylphosphinoxy, etc.                                          Si     trimethysilyl, dimethylbutylsilyl, dimethylbenzylsilyl,                       dimethylvinylsilyl, dimethylallylsilyl, etc.                       ______________________________________                                    

As employed herein, the delivery-enhancing group refers to one whichattaches or substantively, adhesively, cohesively or otherwise bonds theAEA (carrying the antibacterial agent) to oral (e.g. tooth and gum)surfaces, thereby "delivering" the antibacterial agent to such surfaces.The organic retention-enhancing group, generally hydrophobic, attachesor otherwise bonds the antibacterial agent to the AEA, thereby promotingretention of the antibacterial agent to the AEA and indirectly on theoral surfaces. In some instances, attachment of the antibacterial agentoccurs through physical entrapment thereof by the AEA, especially whenthe AEA is a cross-linked polymer, the structure of which inherentlyprovides increased sites for such entrapment. The presence of a highermolecular weight, ore hydrophobic cross-linking moiety in thecross-linked polymer still further promotes the physical entrapment ofthe antibacterial agent to or by the cross-linked AEA polymer.

Preferably, the AEA is an anionic polymer comprising a chain or backbonecontaining repeating units each preferably containing at least onecarbon atom and preferably at least one directly or indirectly pendant,monovalent delivery-enhancing group and at least one directly orindirectly pendant monovalent retention-enhancing group geminally,vicinally or less preferably otherwise bonded to atoms, preferablycarbon, in the chain. Less preferably, the polymer may containdelivery-enhancing groups and/or retention-enhancing groups and/or otherdivalent atoms or groups as links in the polymer chain instead of or inaddition to carbon atoms, or a cross-linking moieties.

It will be understood that any examples or illustrations of AEA'sdisclosed herein which do not contain both delivery-enhancing groups andretention enhancing groups may and preferably should be chemicallymodified in known manner to obtain the preferred AEA's containing bothsuch groups and preferably a plurality of each such groups. In the caseof the preferred polymeric AEA's, it is desirable, for maximizingsubstantivity and delivery of the antibacterial agent to oral surfaces,that the repeating units in the polymer chain or backbone containing theacidic delivery enhancing groups constitute at least about 10%,preferably at least about 50%, more preferably at least about 80% up to95% or 100% by weight of the polymer.

According to a preferred embodiment of this invention, the AEA comprisesa polymer containing repeating units in which one or more phosphonicacid delivery-enhancing groups are bonded to one or more carbon atoms inthe polymer chain. An example of such an AEA is poly (vinyl phosphonicacid) containing units of the formula: ##STR1## which however does notcontain a retention-enhancing group. A group of the latter type wouldhowever be present in poly (1-phosphonopropene) with units of theformula: ##STR2## A preferred phosphonic acid-containing AEA for useherein is poly (beta styrene phosphonic acid) containing units of theformula: ##STR3## wherein Ph is phenyl, the phosphonicdelivery-enhancing group and the phenyl retention-enhancing group beingbonded on vicinal carbon atoms in the chain, or a copolymer of betastyrene phosphonic acid with vinyl phosophonyl chloride having the unitsof the foregoing formula III alternating or in random association withunits of formula I above, or poly (alpha styrene phosphonic acid)containing units of the formula:: ##STR4## in which the delivery--andretention--enhancing groups are geminally bonded to the chain.

These styrene phosphonic acid polymers and their copolymers with otherinert ethylenically unsaturated monomers generally have molecularweights in the range of about 2,000 to about 30,000, preferably about2,500 to about 10,000, and are, with their methods of preparationdisclosed and claimed in concurrently filed application Ser. No.398,606, which disclosure is incorporated here. Such "inert" monomers donot significantly interfere with the intended function of any copolymeremployed as an AEA herein.

Other phosphonic-containing polymers include, for example, phosphonatedethylene having units of the formula.

    --[CH.sub.2 ].sub.14 CHPO.sub.3 H.sub.2 ].sub.n --         V

where n may for example be an integer or have a value giving the polymera molecular weight of about 3,000; and sodium poly[butene-4,4-diphosphonate) having units of the formula: ##STR5## poly(allyl bis (phosphonoethyl) amine) having units of the formula: ##STR6##Other phosphonated polymers, for example poly (ally phosphono acetate),phosphonated polymethacrylate, etc. and the geminal diphosphonatepolymers disclosed in EP Publication 0321233 may be employed herein asAEA's, provided of course that they contain or are modified to containthe above-defined organic retention-enhancing groups.

Although not used in the present invention to coact with polyphosphateanticalculus agent, synthetic anionic polymeric polycarboxylate having amolecular weight of about 1,000 to about 1,000,000, preferably about30,000 to about 500,000, has been used as an inhibitor of alkalinephosphatase enzyme in optimizing anticalculus effectiveness of linearmolecularly dehydrated polyphsophate salts, as disclosed in U.S. Pat.No. 4,627,977 to Gaffar et al. Indeed, in published British PatentPublication 22 00551, the polymeric polycarboxylate is disclosed as anoptional ingredient in oral compositions containing linear molecularlydehydrated polyphosphate salts and substantially water-insolublenoncationic antibacterial agent. It is further observed, in the contextof the present invention that such polycarboxylate is markedly effectiveto enhance delivery and retention of the noncationic antibacterial,antiplaque agent to dental surfaces when another ingredient with whichthe polymeric polycarboxylate would coact (that is, molecularlydehydrated polyphosphate) is absent; for instance, when the ingredientwith which the polymeric polycarboxylate coacts is especially thenoncationic antibacterial agent.

Synthetic anionic polymeric polycarboxylates and their complexes withvarious cationic germicides, zinc and magnesium have been previouslydisclosed as anticalculus agents per se in, for example U.S. Pat. No.3,429,963 to Shedlovsky; U.S. Pat. No. 4,152,420 to Gaffar; U.S. Pat.No. 3,956,480 to Dichter et al; U.S. Pat. No. 4,138,477 to Gaffar; andU.S. Pat. No. 4,183,914 to Gaffar et al. It is to be understood that thesynthetic anionic polymeric polycarboxylates so disclosed in theseseveral patents when containing or modified to contain the above-definedretention-enhancing groups are operative as AEA's in the compositionsand methods of this invention and such disclosures are to that extentincorporated herein by reference thereto.

These synthetic anionic polymeric polycarboxylates are often employed inthe form of their free acids or preferably partially or more preferablyfully neutralized water soluble or water-swellable (hydratable,gel-forming) alkali metal (e.g. potassium and preferably sodium) orammonium salts. Preferred are 1:4 to 4:1 copolymers of maleic anhydrideor acid with another polymerizable ethylenically unsaturated monomer,preferably methyl vinyl ether (maleic anhydride) having a molecularweight (M.W.) of about 30,000 to about 1,000,000, most preferably about30,000 to about 500,000. These copolymers are available for example asGantrez, e.g. AN 139 (M.W. 500,000). A.N. 119 (M.W. 250,000); andpreferably S-97 Pharmaceutical Grade (M.W. 70,000), of GAF Corporation.

Other AEA-operative polymeric polycarboxylates containing or modified tocontain retention-enhancing groups include those disclosed in U.S. Pat.No. 3,956,480 referred to above, such as the 1:1 copolymers of maleicanhydride with ethyl acrylate, hydroxyethyl methacrylate,N-vinyl-2-pyrollidone, or ethylene, the latter being available forexample as Monsanto EMA No. 1103 M.W. 10,000 and EMA Grade 61, and 1:1copolymers of acrylic acid with methyl or hydroxyethyl methacrylate,methyl or ethyl acrylate, isobutyl, isobutyl vinyl ether orN-vinyl-2-pyrrolidone.

Additional operative polymeric polycarboxylates disclosed in abovereferred to U.S. Pat. Nos. 4,138,477 and 4,183,914 containing ormodified to contain retention-enhancing groups, include copolymers ofmaleic anhydride with styrene, isobutylene or ethyl vinyl ether,polyacrylic, polyitaconic and polymaleic acids, and sulfoacrylicoligomers of M.W. as low as 1,000, available as Uniroyal ND-2.

Suitable generally are retention-enhancing group-containing polymerizedolefinically or ethylenically unsaturated carboxylic acids containing anactivated carbon-to-carbon olefinic double bond which readily functionsin polymerization because of its presence in the monomer molecule eitherin the alpha-beta position with respect to a carboxyl group or a part ofa terminal methylene grouping. Illustrative of such acids are acrylic,methacrylic, ethacrylic, alpha-chloroacrylic, crontonic, beta-acryloxypropionic, sorbic, alpha-chlorsorbic, cinnamic, beta-styrylacrylic,muconic, itaconic, citraconic, mesaconic, glutaconic, aconitic,alpha-phenylacrylic, 2-benzyl acrylic, 2-cyclohexylacrylic, angelic,umbellic, fumaric, maleic acids and anhydrides. Other different olefinicmonomer copolymerizable with such carboxylic monomers includvinylacetate, vinyl chloride, dimethyl maleate and the like. Copolymersordinarily contain sufficient carboxylic salt groups forwater-solubility.

Also useful herein are so-called carboxyvinyl polymers disclosed astoothpaste components in U.S. Pat. No. 3,980,767 to Chown et al; U.S.Pat. No. 3,935,306 to Roberts et al; U.S. Pat. No. 3,919,409 to Perla etal; U.S. Pat. No. 3,911,904 to Harrison, and U.S. Pat. No. 3,711,604 toColodney et al. They are commercially available for example under thetrademarks Carbopol 934, 940 and 941 of B. F. Goodrich, these productsconsisting essentially of a colloidally water-soluble polymer ofpolyacrylic acid crosslinked with from about 0.75% to about 2.0% ofpolyally sucrose or polyally pentaerythritol as cross linking agent, thecross-linked structures and linkages in these and other cross-linkedpolymeric AEA's, providing the desired retention enhancement byhydrophobicity when adequate, and/or physical entrapment of theantibacterial agent. Polycarbophil, being polyacrylic cross-linked withless than 0.1% divinyl glycol, the lower proportion, molecular weight,and/or hydrophobicity of this cross-linking agent tending to providedecreased or no retention enhancement 2,5-dimethyl-1,5-hexadiane,exemplifies a more effective retention-enhancing cross-linking agent.

The synthetic anionic polymeric polycarboxylate component is most oftena hydrocarbon with option halogen and O-containing substituents andlinkages as present in for example ester, ether and OH groups, and isemployed in the instant compositions in approximate weight amounts of0.05 to 4%, preferably 0.05 to 3%, more preferably 0.1 to 2%.

The AEA may also comprise natural anionic polymeric polycarboxylatescontaining retention-enhancing groups. Carboxymethyl cellulose and otherbinding agents gums and film-formers devoid of the above-defineddelivery-enhancing and/or retention-enhancing groups are ineffective asAEA's.

As illustrative of AEA's containing phosphinic acid and/or sulfonic aciddelivery enhancing groups, there may be mentioned polymers andcopolymers containing units or moieties derived from the polymerizationof vinyl or allyl phosphinic and/or sulfonic acids substituted as neededon the 1 or 2 (or 3) carbon atom by an organic retention-enhancinggroup, for example having the formula --(X)_(n) --R defined above.Mixtures of these monomers may be employed, and copolymers thereof withone or more inert polymerizable thylenically unsaturated monomers suchas those described above with respect to the operative synthetic anionicpolymeric polycarboxylates. As will be noted, in these and otherpolymeric AEA's operative herein, usually only one acidicdelivery-enhancing group is bonded to any given carbon or other atom inthe polymer backbone or branch thereon. Polysiloxanes containing ormodified to contain pendant delivery-enhancing groups and retentionenhancing groups may also be employed as AEA's herein. Also effective asAEA's herein are ionomers containing or modified to contain delivery-and retention-enhancing groups. Ionomers are described on pages 546-573of the Kirk-Othmer Encyclopedia of Chemical Technology, third edition,Supplement Volume, John Wiley & Sons, Inc., copywright 1984, whichdescription is incorporated herein by reference. Also effective as AEA'sherein, provided they contain or are modified to containretention-enhancing groups, are polyesters, polyurethanes and syntheticand natural polyamides including proteins and proteinaceous materialssuch as collagen, poly (argenine) and other polymerized amino acids.

Without being bound to a theory, it is believed that the AEA, especiallypolymeric AEA is most often and desirably an anionic film formingmaterial and is thought to attach to tooth surfaces and form acontinuous film over the surfaces, thereby preventing bacterialattachment to tooth surfaces. It is possible that the noncationicantibacterial agent forms a complex or other form of association withthe AEA, thus forming a film of a complex or the like over toothsurfaces. The enhanced delivery and film forming property of the AEA andthe enhanced delivery and retention of the antibacterial agent on toothsurfaces due to the AEA appears to make tooth surfaces unfavorable forbacterial accumulation particularly since the direct bacteriostaticaction of the antibacterial agent controls bacterial growth. Therefore,through the combination of three modes of actions: 1) enhanced delivery,2) long retention time on tooth surfaces, and 3) prevention of bacterialattachment to tooth surfaces, the oral composition is made efficaciousfor reducing plaque. Similar effectiveness is attained on soft oraltissue at or near the gum line.

In aforementioned application Ser. No. 398,606 filed on even data,titled "Antibacterial Antiplaque Oral Composition" wherein thedentifrices thereof contain about 5-30% by weight of a siliceouspolishing agent, a material which solubilizes the noncationicantibacterial agent to render it effective in delivery to soft oraltissues at the gum line is employed. In the present invention, whereinabout 30-75% by weight of a dentally acceptable water-insolublepolishing agent is present, it is found that the solubilizing materialis not required; but is rather optional.

In the oral preparation dentifrice, an orally acceptable vehicleincluding a water-phase with humectant is present. The humectant ispreferably glycerine and/or sorbitol. Water is present typically inamount of about 15-35% or 40% by weight and glycerine and/or sorbitoltypically total about 20-75% by weight of the oral preparationdentifrice, more typically about 25-60%. Reference hereto to sorbitolrefers to the material typically as available commercially in 70%aqueous solutions. The optional ingredients which assist solubilizationof the antibacterial agent in saliva are typically incorporated in thewater-humectant phase in amount of about 0.5-20% by weight. Theseoptional solubilizing agents include humectant polyols such propyleneglycol, dipropylene glycol and hexylene glycol, cellosolves such asmethyl cellosolve and ethyl cellosolve, vegetable oils and waxescontaining at least about 12 carbons in a straight chain such as oliveoil, castor oil and petrolatum and esters such as amyl acetate, ethylacetate and benzyl benzoate. As used herein, "propylene glycol" includes1,2-propylene glycol and 1,3-propylene glycol. Significant amounts ofpolyethylene glycol particularly of molecular weight of 600 or moreshould be avoided since polythylene glycol effectively inhibits theantibacterial activity of the noncationic antibacterial agent. Forinstance, polyethylene glycol (PEG) 600 when present with tricolosan ina weight ratio of 25 triclosan: 1 PEG 600 can reduce the antibacterialactivity of triclosan by a factor of about 16 from that prevailing inthe absence of the polyethylene glycol.

The pH of such oral preparation dentifrice of the invention is generallyin the range of about 4.5 to about 9 or 10 and preferably about 6.5 toabout 7.5. It is noteworthy that the compositions of the invention maybe applied orally at a pH below 5 without substantially decalcifying orotherwise damaging dental enamel. The pH can be controlled with acid(e.g. citric acid or benzoic acid) or base (e.g. sodium hydroxide) orbuffered (as with sodium citrate, benzoate, carbonate, or bicarbonate,disodium hydrogen phosphate, sodium dihydrogen phosphate, etc.).

In this invention, the oral composition dentifrice may be substantiallypasty in character, such as a tooth paste (dental cream), although whensiliceous polishing agent is employed (which is not generally the case,since such material is typically not employed in amount above about 30%by weight) it can be gel in character. The vehicle of the oralcomposition dentifrice contains dentally acceptable polishing material,examples of which polishing materials are water-insoluble sodiummetaphosphate, potassium metaphosphate, tricalcium phosophate,dihydrated dicalcium phosphate, anhydrous dicalcium phosphate, calciumpyrophosphate, magnesium orthophosphate, trimagnesium phosphate, calciumcarbonate, aluminum silicate, hydrated alumina, silica, bentonite, andmixtures thereof with each other or with hard polishing materials suchas calcined alumina and zirconium silicate, material including theparticulate thermosetting resins described in U.S. Pat. No. 3,070,510issued Dec. 15, 1962, such as melamine, phenolic, andurea-formaldehydes, and cross-linked polyeposices and polyesters.Preferred polishing materials include insoluble sodium metaphosphates,dicalcium phosphate and hydrated alumina.

Many of the so-called "water-insoluble" polishing materials are anionicin character and also include small amounts of soluble material. Thus,insoluble sodium metaphosphate may be formed in any suitable manner asillustated by Thorpe's Dictionary of Applied Chemistry, Volume 9, 4thEdition, pp. 510-511. The forms of insoluble sodium metaphosphate knownas Madrell's salt and Kurrol's salt are further examples of suitablematerials. These metaphosphate salts exhibit only a minute solubility inwater, and therefore are commonly referred to as insolublemetaphosphates (IMP). There is present therein a minor amount of solublephosphate material as impurities, usually a few percent such as up to 4%by weight. The amount of soluble phosphate material, which is believedto include a soluble sodium trimetaphosphate in the case of insolublemetaphosphate, may be reduced or eliminated by washing with water ifdesired. The insoluble alkali metal metaphosphate is typically employedin powder form of a particle size such that no more than 1% of thematerial is larger than 37 microns.

Hydrated alumina is an example of a polishing material which isessentially nonionic in nature. Typically, it is small in particle size,i.e., at least about 85% of the particles are smaller than 20 micronsand is such as that classified as gibbsite (alpha alumina trihydrate)and normally represented chemically as Al₂ O₃.3H₂ O or Al(OH)₃. Theaverage particle size of gibbsite is generally about 6 to 9 microns. Atypical grade has the following size distribution:

    ______________________________________                                                Micron                                                                              Percent                                                         ______________________________________                                                <30   94-99                                                                   <20   85-93                                                                   <10   56-67                                                                   <5    28-40                                                           ______________________________________                                    

The polishing material is generally present in the cream, paste or gelcompositions in weight amounts of about 30% to about 75%.

Toothpastes or dental cream typically contain a natural or syntheticthickener or gelling agent in proportions of about 0.1 to about 10%,preferably about 0.5 to about 5%. A suitable thickener is synthetichectorite, a synthetic colloidal magnesium alkali metal silicate complexclay available for example as Laponite (e.g. CP, SP 2002, D) marketed byLaporte Industries Limited. Laponite D analysis shows, approximately byweight, 58.00% SiO₂, 25.40% MgO, 3.05% Na₂ O, 0.98% Li₂ O), and somewater and trace metals. Its true specific gravity is 2.53 and it has anapparent bulk density (g./ml. at 8% moisture) of 1.0.

Other suitable thickeners or gelling agents include Irish moss,iotacarrageenan, gum tragacanth, starch, polyvinylpyrrolidone,hydroxyethpropyl-cellulose, hydroxybutyl methyl cellulose, hydroxypropylmethyl cellulose, hydroxyethyl cellulose (e.g. available as Natrosol)and sodium carboxymethyl cellulose.

Without being bound to a theory whereby the advantages of this inventionare achieved, it is believed that an aqueous, humectant vehicle isnormally solubilized in the surfactant micelles in the mobile, e.g.liquid, phase (that is, not including gelling agent and polishing agent)of a dentrifice formula. The mobile phase solution of dentifrice duringuse can become diluted with saliva and a portion of the antibacterialagent, e.g. triclosan, could precipitate out. However, when the amountof polishing agent is 30% by weight or more of the oral compositiondentifrice, the amount of triclosan soluble in the mobile phase issufficient to provide substantial antiplaque effect on soft oral tissuesas well as on dental surfaces. This effect can be increased, if desired,if a solubilizing material compatible with the antibacteral agent whichincreases its solubility in saliva is present. In this regard it isnoted that the solubilizing agent propylene glycol is widely used indrug delivery systems, for instance, in European Patent Publication0271,332 for its strong interaction with biological membranes. It isexpected that triclosan is partitioned from aqueous environment intopropylene glycol and surfactant emulsions during use and further thatpropylene glycol in bulk phase allows greater probability of triclosanemergence out of surfactant micelles, thereby rendering triclosan morecompletely available for delivery into bacterial and soft surfaces aswell as onto tooth surfaces. Similar remarks apply to other waterinsoluble noncationic antibacterial agents herein described.

The oral composition dentifrice may also contain an anticaries amount ofa fluoride ion source sufficient to supply about 25 ppm to 5000 ppm offluoride ions.

The sources of fluoride ions, or fluoride-providing component are wellknown in the art as anti-caries agents. These compounds may be slightlysoluble in water or may be fully water-soluble. They are characterizedby their ability to release fluoride ions in water and by substantialfreedom from undesired reaction with other compounds of the oralpreparation. Among these materials are inorganic fluoride salts, such assoluble alkali metal, alkaline earth metal salts, for example sodiumfluoride, potassium fluoride, ammonium fluoride, calcium fluoride, acopper fluoride such as cuprous fluoride, zinc fluoride, bariumfluoride, sodium fluorosilicate, ammonium fluorosilicate, sodiumfluorozirconate, ammonium fluorozirconate, sodium monofluorphosphate,aluminum mono- and di-fluorophosphate, and fluorinated sodium calciumpyrophosphate. Alkali metal and tin fluorides, such as sodium andstannous fluorides, sodium monofluorophosphate (MFP) and mixturesthereof, are preferred.

The amount of fluorine-providing compound is dependent to some extentupon the type of compound, its solubility, and the type of oralpreparation, but it must be a non-toxic amount, generally about 0.0005to about 3.0% in the preparation. In a dentifrice preparation, an amountof such compound which releases up to about 5,000 ppm of F ion by weightof the preparation is considered satisfactory. Any suitable minimumamount of such compound may be used, but it is preferable to employsufficent compound to release about 300 to 2,000 ppm, more preferablyabout 800 to about 1,500 ppm of fluoride ion.

Typically, in the cases of alkali metal fluorides, this component ispresent in an amount up to about 2% by weight, based on the weight ofthe preparation, and preferably in the range of about 0.05% to 1%. Inthe case of sodium monofluorophosphate, the compound may be the presentin an amount of about 0.1-3%, more typically about 0.76%.

It will be understood that, as is conventional, the oral preparationsare to be sold or otherwise distributed in suitable labelled packages.Thus a toothpaste or cream will usually be in a collapsible tubetypically aluminum, lined lead or plastic, or other squeeze, pump orpressurized dispenser for metering out the contents, having a labeldescribing it, in substance, as a toothpaste, dental cream or the like.

Organic surface-active agents are used in the compositions of thepresent invention to achieve increased prophylactic action. Moreover,they assist in achieving thorough and complete dispersion of theanticalculus agent and antiplaque agent throughout the oral cavity, andrender the instant compositions more cosmetically acceptable. Indeed, atleast one of surface-active agent or flavoring oil is present to effectdesired solubilization of the antibacterial agent. The organicsurface-active material is preferably anionic, nonionic or ampholytic innature, and it is preferred to employ as the surface-active agent adetersive material which imparts to the composition detersive andfoaming properties. Suitable examples of anionic surfactants arewater-soluble salts of higher fatty acid monoglyceride monosulfates,such as the sodium salt of the monosulfated monoglyceride ofhydrogenated coconut oil fatty acids, higher alkyl sulfates such assodium lauryl sulfate, alkyl aryl sulfonates such as sodium dodecylbenzene sulfonate, higher alkyl sulfoacetates, higher fatty acid estersof 1,2-dihydroxy propane sulfonate, and the substantially saturatedhigher sliphatic acyl amides of lower aliphatic amino carboxylic acidcompounds, such as those having 12 to 16 carbons in the fatty acid,alkyl or acyl radicals, and the like. Examples of the last mentionedamides are N-lauroyl sarcosine, and the sodium, potassium, andethanolamine salts of N-lauroyl, N-myristoyl, or N-palmitoyl sarcosinewhich should be substantially free from soap or similar higher fattyacid material. The use of these sarcosinate compounds in the oralcompositions of the present invention is particularly advantageous sincethese materials exhibit a prolonged a marked effect in the inhibition ofacid formation in the oral cavity due to carbohydrates breakdown inaddition to exerting some reduction in the solubility of tooth enamel inacid solutions. Examples of water-soluble nonionic surfactants arecondensation products of ethylene oxide with various reactivehydrogen-containing compounds reactive therewith having long hydrophobicchains (e.g. aliphatic chains of about 12 to 20 carbon atoms), whichcondensation products ("ethoxamers") contain hydrophilic polyoxyethylenemoieties, such as condensation products of poly(ethylene oxide) withfatty acids, fatty alcohols, fatty amides, polyhydric alcohols (e.g.sorbitan monostearate) and polypropyleneoxide (e.g. Pluronic materials).

Surface active agent is typically present in amount of about 0.5-5% byweight, preferably about 1-2.5%. As indicated, surface active agent isbelieved to assist in the dissolving of the noncationic antibacterialagents.

Various other materials may be incorporated in the oral preparations ofthis invention such as whitening agents, preservatives, silicones,chlorophyll compounds and/or ammoniated material such as urea,diammonium phosphate, and mixtures thereof. These adjuvants, wherepresent, are incorporated in the preparations in amounts which do notsubstantially adversely affect the properties and characteristicsdesired. Significant amounts of zinc, magnesium and other metal saltsand materials, generally soluble, which would complex with activecomponents of the instant invention are to be avoided.

Any suitable flavoring or sweetening material may also be employed.Examples of suitable flavoring constituents are flavoring oils, e.g. oilof spearmint, peppermint, wintergreen, sassafras, clove, sage,eucalyptus, margoram, cinnamon, lemon, and orange, and methylsalicylate. Suitable sweetening agents include sucrose, lactose,maltose, sorbitol, xylitol, sodium cyclamate, perillartine, AMP(aspartyl phenyl alanine, methyl ester), saccharine and the like.Suitably, flavor and sweetening agents each or together comprise fromabout 0.1% to 5% more of the preparation. Moreover, flavor oil isbelieved to aid the dissolving of the antibacterial agent together withor even in the absence of surface-active agent.

In the preferred practice of this invention an oral compositioncontaining the composition of the present invention is preferablyapplied regularly to dental enamel, such as every day or every second orthird day or preferably from 1 to 3 times daily, at a pH of about 4.5 toabout 9, generally about 5.5 to about 8, preferably about 6 to 8, for atleast 2 weeks up to 8 weeks or more up to lifetime.

The compositions of this invention can be incorporated in lozenges, orin chewing gum or other products, e.g. by stirring into a warm gum baseor coating the outer surface of a gum base, illustrative of which may bementioned jelutong, rubber latex, vinylite resins, etc., desirably withconventional plasticizers of softeners, sugar or other sweeteners orcarbohydrates such as glucose, sorbitol and the like.

The following examples are further illustrative of the nature of thepresent invention, but it is understood that the invention is notlimited thereto. All amounts and proportions referred to herein and inthe appended claims are by weight, unless otherwise indicated.

EXAMPLE 1

The following dentifrice is prepared:

    ______________________________________                                                         Parts                                                                         A     B        C                                             ______________________________________                                        Alpha Alumina Trihydrate                                                                         48.00   48.00    48.00                                     Propylene Glycol   --      0.50     0.50                                      Sorbitol (70%)     21.70   21.70    21.70                                     Gantrez S-97 (13% solution)                                                                      15.00   15.00    --                                        Gantrez S-97 (powder)                                                                            --      --       2.00                                      Sodium Lauryl Sulfate                                                                            2.00    2.13     2.13                                      Sodium Saccharine  0.30    0.30     0.30                                      Sodium Hyroxide (50%)                                                                            1.20    1.20     1.20                                      Flavor Oil         0.95    0.95     0.95                                      Irish Moss         1.00    --       --                                        Sodium carboxymethyl celluose                                                                    --      1.00     1.00                                      Sodium monofluorophosphate                                                                       0.76    0.76     0.76                                      Titanium Dioxide   --      0.50     0.50                                      Triclosan          0.30    0.30     0.30                                      Water              Q.S. to Q.S. to  Q.S. to                                                      100.00  100.00   100.00                                    ______________________________________                                    

The foregoing dentifrices deliver triclosan to the teeth and soft tissueareas of the gums substantially more effectively than correspondingdentifrices in which the Gantrez polycarboxylate is absent.

EXAMPLE 2

The following dentifrices are prepared:

    ______________________________________                                                         Parts                                                        ______________________________________                                        Glycerine          22.00      10.00                                           Sorbitol (70%)     --         17.00                                           Sodium Carboxymethyl cellulose                                                                   1.00       1.00                                            Gantrez S-97       2.00       2.00                                            Sodium Saccharin   0.20       0.20                                            Sodium Benzoate    0.50       0.50                                            Sodium Monofluorophsophate                                                                       0.76       0.76                                            Dicalcium Phosphate Dihydrate                                                                    48.76      48.76                                           Triclosan          0.30       0.30                                            Sodium Lauryl Sulfate                                                                            1.20       1.20                                            Flavor Oil         0.89       0.89                                            Water              Q.S. to 100.00                                                                           Q.S. to 100.00                                  ______________________________________                                    

The foregoing dentifrices deliver triclosan to saliva coatedhydroxyapatite disk more effectively than corresponding dentifrices inwhich the Gantrez polycarboxylate is absent.

EXAMPLE 3

The following antiplaque dentifrice is prepared:

    ______________________________________                                                                  Parts                                               ______________________________________                                        Glycerine                   15.00                                             Propylene Glycol            2.00                                              Sodium Carboxymethyl cellulose                                                                            1.50                                              Water                       24.93                                             Vinyl Methyl Ether/Maleic Anhydride copolymer                                                             4.76                                              (42% solution)                                                                Sodium Monofluorophosphate  0.76                                              Sodium Saccharin            0.30                                              Insoluble Sodium Metaphosphate                                                                            47.00                                             Titanium Dioxide            0.50                                              Sodium Lauryl Sulfate       2.00                                              Triclosan                   0.95                                              Flavor Oil                  0.95                                              ______________________________________                                    

In the foregoing Examples improved results are also achievable whentriclosan is replaced with each of phenol, 2,2'-methylene bis(4-chloro-6-Bromophenol), eugenol and thymol, and/or when Gantrez isreplaced by other AEA's such as Carbopols (e.g. 934), or styrenephosphonic acid polkymers having molecular weights within the range ofabout 3,000 to 10,000 such as poly (beta-styrenephosphonic acid),copolymers of vinyl phosphonic acid with beta-styrenephosphonic acid,and poly (alpha-styrenephosphonic acid), or sulfoacrylic oligomers, or a1:1 copolymer of maleic anhydride with ethyl acrylate.

EXAMPLE 4

Dentifrice Mobile Phases Containing Triclosan

    ______________________________________                                                        Composition, % w/w                                            Components        A         B                                                 ______________________________________                                        Sorbitol (70%)    53.33     40.00                                             Water             40.48     39.15                                             Gantrez S (15%)   --        13.33                                             NaOH (50%)                  1.33                                              Sodium Pyrophosphate                                                                            --        --                                                Potassium Pyrophosphate                                                                         --        --                                                Saccharin         0.40      0.40                                              Sodium Fluoride   0.32      0.32                                              Flavor Oil        1.47      1.47                                              Sodium Lauryl Sulfate                                                                           3.33      3.33                                              Triclosan         0.67      0.67                                              ______________________________________                                    

The Concentration of the above components are 1.33% dentifrice level toreflect 25% level of abrasive which may be needed to make a completedentifrice.

The above mobile phases of the indicated dentifrice formulations aretested for triclosan uptake on saliva coated HA disks following thestandard procedure described in assignee's said concurrently filed Ser.No. 398,605. Results are shown in Table I below.

                  TABLE I                                                         ______________________________________                                        Uptake of triclosan by Saliva Coated Hydroxyapatite (HA)                      Disks from Diluted and Undiluted Dentifrice Mobile Phases.                                      A     B                                                     ______________________________________                                        % Triclosan         0.67    0.67                                              Ionic Strength (M/L)                                                                              0.375   --                                                (calculated)                                                                  pH                  8.7     7.6                                               Triclosan Uptake (ug/disk)                                                                        55      122                                               Undiluted                                                                     ______________________________________                                    

The above results show a greater then two fold increase in triclosanuptake achieved with the B formulation containing Gantrez relative tothe A formulation without the Gantrez.

EXAMPLE 5

Concentration and Uptake of Triclosan by HA from Supernatant of 1:1Dentifrice/Water Slurries.

    ______________________________________                                        Dentifrice Containing                                                                          Trilosan (ug/ml) in                                                                         Trilosan                                       0.5% Triclosan, 2.5%                                                                           Supernatant of 1:1                                                                          Uptake                                         Sodium, and Lauryl Sulfate                                                                     Slurry        pg/disk                                        ______________________________________                                        25% Hydrated Silica +                                                                          1,650         52                                             1.5% Gantrez S-97                                                             50% Alumina, +   1.905         74                                             1.5% Gantrez S-97                                                             ______________________________________                                    

Supernatents of 1:1 Dentifrice/Water slurries of the above dentifricesare tested for concentraton of the triclosan in the supernatant and fortriclosan uptake on saliva coated HA disks. The results indicate thatusing 50% alumina abrasive increases the triclosan substantially underlow 1:1 dilution conditions (from 1,650 to 1,905), resulting in asubstantial increase in the triclosan uptake (from 52 to 74).

This invention has been described with respect to certain preferredembodiments and it will be understood that modifications and variationsthereof obvious to those skilled in the art are to be included withinthe purview of this application and the scope of the appended claims.

We claim:
 1. An oral composition dentifrice for attaching, adhering orbonding a plaque-inhabiting antibacterial agent to oral tooth and gumsurfaces comprising in an orally acceptable aqueous humectant vehicleabout 30-75% by weight of a dentally acceptable water insolublepolishing agent, an effective antiplaque amount in the range of about0.01-5% by weight of a substantially water insoluble non-cationicantibacterial agent, at least one of a surface active agent or aflavoring oil and an effective amount in the range of about 0.05-4% byweight of an antibacterial-enhancing agent which contains at least onedelivery-enhancing functional group and at least one organicretention-enhancing group, which delivery-enhancing group enhancesdelivery of said antibacterial agent to oral tooth and gum surfaces andsaid retention-enhancing group enhances attachment, adherence or bondingof said antibacterial agent on oral tooth and gum surfaces, wherein saidoral composition is free of polyphosphate anticalculus agent in aneffective anticalculus amount and said vehicle is other thanpolyethylene glycol which reduces the antibacterial activity of saidantibacterial agent.
 2. The oral composition claimed in claim 1, whereinsaid antibacterial agent is selected from the group consisting ofhalogenated diphenyl ethers, halogenated salicylanilides, benzoicesters, halogenated carbanilides and phenolic compounds.
 3. The oralcomposition claimed in claim 2, wherein said antibacterial agent is ahalogenated diphenyl ether.
 4. The oral composition claimed in claim 3,wherein said halogenated diphenyl ether is2,4,4'-trichloro-2'-hydroxydiphenyl ether.
 5. The oral compositionclaimed in claim 2, wherein said antibacterial agent is a phenoliccompound.
 6. The oral composition claimed in claim 5, wherein saidphenolic compound is selected from the group consisting of phenol,thymol, eugenol, and 2,2'-methylene bis (4-chloro-6-bromophenol).
 7. Theoral composition claimed in claim 1, wherein said antibacterial agent ispresent in amount of about 0.25-5% by weight.
 8. The oral compositionclaimed in any one of claims 1-7, wherein said polishing agent isselected from the group consisting of sodium metaphosphate, tricalciumphosphate, dihydrated dicalcium phosphate, anhydrous dicalciumphosphate, calcium pyrophosphate, magnesium orthophosphate, trimagnesiumphosphate, calcium carbonate, aluminum silicate, hydrated alumina,silica, bentonite, and mixtures thereof.
 9. The oral compositiondentifrice claimed in claim 8, wherein said polishing agent is dicalciumphosphate dihydrate.
 10. The oral composition dentifrice claimed inclaim 8, wherein said polishing agent is hydrated alumina.
 11. The oralcomposition claimed in any one of claims 1-7, wherein said surfaceactive agent is present in amount of about 0.5.5% by weight.
 12. Theoral composition dentifrice claimed in claim 11, wherein said surfaceactive agent is present in amount of about 1-2.5% by weight.
 13. Theoral composition dentifrice claimed in claim 1, wherein saidantibacterial-enhancing agent is water soluble or swellable.
 14. Theoral composition claimed in claim 13, wherein saidantibacterial-enhancing agent has an average molecular weight of about100 to about 1,000,000.
 15. The oral composition claimed in claim 14,wherein said delivery-enhancing group is acidic.
 16. The oralcomposition claimed in claim 15, wherein said delivery-enhancing groupis selected from the group consisting of carboxylic, phosphinic andsulfonic acids, and their salts, and mixtures thereof, and wherein saidorganic retention-enhancing group comprises the formula --(X)_(n) --Rwherein X is O, N, S, SO, SO₂, P, PO or Si, R is hydrophobic alkyl,alkenyl, acyl, aryl, alkaryl, aralkyl, heterocyclic, or theirinert-substituted derivatives, and n is zero or one or more, and whereinsaid antibacterial-enhancing agent is a monomer or polymer selected fromthe group consisting of oligomers, homopolymers, copolymers of two ormore monomers, ionomers, block copolymers, graft copolymers, andcrosslinked polymers and monomers.
 17. The oral composition claimed inclaim 16, wherein said antibacterial-enhancing agent is an anionicpolymer containing a plurality of said delivery-enhancing andretention-enhancing groups.
 18. The oral composition claimed in claim17, wherein said anionic polymer comprises a chain containing repeatingunits each containing at least one carbon atom.
 19. The oral compositionclaimed in claim 18, wherein each unit contains at least onedelivery-enhancing group and at least one organic retention-enhancinggroup and at least one organic retention-enhancing group bonded to thesame or vicinal or other atoms in the chain.
 20. The oral compositionclaimed in claim 16, wherein the delivery-enhancing group is acarboxylic group salt thereof.
 21. The oral composition dentifrice forattaching, adhering or bonding a plaque-inhibiting antibacterial agentto oral tooth and gum surfaces comprising an orally acceptable aqueoushumectant vehicle, about 30-70% by weight of a dentally acceptable waterinsoluble polishing agent, an effective amount in the range of 0.01-5%by weight of a substantially water insoluble non-cationic antibacterialagent, at least one of surface active agent or a flavoring oil and aneffective amount in the range of about 0.05-4% by weight of an anioniccopolymer of maleic acid or anhydride with another ethylenicallyunsaturated polymerizable monomer, which copolymer enhances delivery andattachment, adherence or bonding of said antibacterial agent on oraltooth and gum surfaces, wherein said oral composition is free ofpolyphosphate anticalculus agent in an effective anticalculus amount andsaid vehicle is other than polyethylene glycol which reduces theantibacterial activity of said antibacterial agent.
 22. The oralcomposition according to claim 21, wherein said other monomer of saidcopolymer is methyl vinyl ether in a 4:1 to 1:4 molar ratio with themaleic acid or anhydride.
 23. The oral composition according to claim22, wherein said copolymer has a molecular weight of about30,000-1,000,000 and is present in amount of about 0.1-2% by weight. 24.A composition according to claim 23, wherein the copolymer has anaverage molecular weight of about 70,000.
 25. The oral compositionclaimed in claim 21, wherein said antibacterial agent is selected fromthe group consisting of halogenated diphenyl ethers, halogenatedsalicylanilides, benzoic ester, halogenated carbanilides, and phenoliccompounds.
 26. A composition according to any one of claims 1-7 and13-25 containing an effective anticaries amount of a fluorideion-providing source.